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Repotrectinib Approved for ROS1-Positive Non–Small Cell Lung Cancer

Repotrectinib skeletal formula.

The FDA has approved repotrectinib (Augtyro, Bristol Myers Squibb Company) for locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC). This is the first approval for the next-generation ROS1/TRK tyrosine kinase inhibitor (TKI) repotrectinib and is the first FDA approval to include patients with ROS1-positive NSCLC who have previously received a ROS1 TKI, as well as patients who are TKI-naive.  

Why it matters: "Repotrectinib is a next-generation ROS1 and TRK TKI that has demonstrated durable activity with a manageable safety profile in TKI-naive and TKI-pretreated patients with advanced ROS1-positive NSCLC," wrote Jessica Jiyeong Lin, MD, an Assistant Professor of Medicine at Harvard Medical School, and colleagues, in their updated results of the TRIDENT-1 trial (NCT03093116), on which approval was based.

What they studied: Safety and efficacy were studied in the phase 1/2, multicenter, single-arm, open-label trial in which a total of 127 patients with ROS1-positive, locally advanced or metastatic NSCLC were enrolled. The trial population included 71 patients with ROS1 TKI–naive patients who had received up to one prior line of platinum-based chemotherapy and/or immunotherapy and 56 patients who had received one prior ROS1 TKI with no prior platinum-based chemotherapy or immunotherapy.

The primary end points measured were overall response rate and duration of response as per RECIST v1.1 as assessed by blinded independent central review.

What they found: Among the 71 ROS1 TKI–naive patients, repotrectinib produced a confirmed overall response rate of 79%, with a median duration of response of 34.1 months. Among the 56 patients who had received prior treatment with a ROS1 inhibitor, the confirmed overall response rate was 38% and the median duration of response was 14.8 months.

Repotrectinib produced responses in intracranial lesions in patients with measurable central nervous system (CNS) metastases and in patients with resistance mutations after receiving TKI therapy.

Adverse events: The most common adverse events experienced by >20% of patients were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness.

Conclusion: "Repotrectinib showed durable clinical activity in ROS1 TKI–naive and –pretreated patients with or without baseline CNS metastases, including intracranial responses," concluded Dr. Lin and colleagues in their abstract presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. "Repotrectinib safety profile was similar in patients with ROS1-positive NSCLC with or without CNS metastases."

Instructions: The recommended dosage of repotrectinib is 160 mg orally once daily, with or without food, for 14 days, followed by an increase to 160 mg twice daily, until disease progression or unacceptable toxicity.

For More Information

Augtyro (repotrectinib) prescribing information will be made available here:

Lin JJ, Drilon AE, Cho BC, et al (2023). Intracranial and systemic efficacy of repotrectinib in advanced ROS1 fusion-positive (ROS1+) non-small cell lung cancer (NSCLC) and central nervous system metastases (CNS mets) in the phase 1/2 TRIDENT-1. J Clin Oncol (ASCO Annual Meeting Abstracts), 41(suppl_16). Abstract 9017. DOI:10.1200/JCO.2023.41.16_suppl.9017

Cho BC, Lin JJ, Camidge DR, et al (2022). Pivotal topline data from the phase 1/2 TRIDENT-1 trial of repotrectinib in patients with ROS1+ advanced non-small cell lung cancer (NSCLC). EJC, 174(suppl_1) S1-2. DOI:10.1016/S0959-8049(22)00812-7 (2023). A study of repotrectinib (TPX-0005) in patients with advanced solid tumors harboring ALK, ROS1, or NTRK1-3 rearrangements (TRIDENT-1). NLM identifier: NCT03093116.

US Food and Drug Administration (2023). FDA approves repotrectinib for ROS1-positive non-small cell lung cancer. Available at:

Image credit: Vaccinationist. Licensed under Public Domain.

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